%0 Case Reports
%T Gerstmann-Sträussler-Scheinker Disease Presenting as Late-Onset Slowly Progressive Spinocerebellar Ataxia, and Comparative Case Series with Neuropathology.
%A Stephen CD
%A de Gusmao CM
%A Srinivasan SR
%A Olsen A
%A Freua F
%A Kok F
%A Montes Garcia Barbosa R
%A Chen JYH
%A Appleby BS
%A Prior T
%A Frosch MP
%A Schmahmann JD
%J Mov Disord Clin Pract
%V 11
%N 4
%D 2024 Apr 23
%M 38258626
%F 4.514
%R 10.1002/mdc3.13976
%X <B>BACKGROUND: </B>Genetic prion diseases, including Gerstmann-Sträussler-Scheinker disease (GSS), are extremely rare, fatal neurodegenerative disorders, often associated with progressive ataxia and cognitive/neuropsychiatric symptoms. GSS typically presents as a rapidly progressive cerebellar ataxia, associated with cognitive decline. Late-onset cases are rare.<BR><B>OBJECTIVE: </B>To compare a novel GSS phenotype with six other cases and present pathological findings from a single case.<BR><B>METHODS: </B>Case series of seven GSS patients, one proceeding to autopsy.<BR><B>RESULTS: </B>Case 1 developed slowly progressive gait difficulties at age 71, mimicking a spinocerebellar ataxia, with a family history of balance problems in old age. Genome sequencing revealed a heterozygous c.392G > A (p.G131E) pathogenic variant and a c.395A > G resulting in p.129 M/V polymorphism in the PRNP gene. Probability analyses considering family history, phenotype, and a similar previously reported point mutation (p.G131V) suggest p.G131E as a new pathogenic variant. Clinical features and imaging of this case are compared with those six additional cases harboring p.P102L mutations. Autopsy findings of a case are described and were consistent with the prion pathology of GSS.<BR><B>CONCLUSIONS: </B>We describe a patient with GSS with a novel p.G131E mutation in the PRNP gene, presenting with a late-onset, slowly progressive phenotype, mimicking a spinocerebellar ataxia, and six additional cases with the typical P102L mutation.